In general, wound healing is any reaction of tissue against damage inflicted upon the tissue, and it is known as a complex biological process comprising chemotaxis, cell differentiation and replication, synthesis of matrix protein, angiogenesis and reconstitution of wound, as a series of tissue repair processes (Steed, D. L. et al., Clin. Plast. Surg. 25:397, 1998). As one of the typical factors for controlling wound healing process, the growth factor may be considered, which regulate cell growth, cell differentiation, cell metabolism and the like through the general wound healing process, as well as the environment around a wound, and have consistently been used for the development of treatment agents. In addition, various kinds of cytokine are known to participate in wound healing. As an example of the cytokine, there is transforming growth factor-β (TGF-β). The TGF-β is involved in the growth and differentiation of various cells. It has been reported that the TGF-β is involved in several complicated functions including growth control, the regulation of immune response, the stimulation of osteogenesis, the induction of cartilage-specific macromolecule and the promotion of wound healing (Bennett, N. T. et al., Am. J. Surg. 165:728, 1993).
According to whether skin deficiency exists or not, a wound may be classified into two types and may be treated with different healing mechanisms. When a wound does not involve skin deficiency, as in most mild injuries, for example a case of having injury only to the epidermis, keratinocytes move from the wound periphery, cover the wound, and reform new epidermis and keratin (Knighton, D. R. and Fiegel, V. D., Invest. Radiol. 26:604-611, 1991). However, when entire skin layers are totally injured or destroyed, new connective tissues, called granulation tissues, fill wound space where regenerated epidermis from the periphery of the wound sites must be covered. The granulation tissues are formed by the deposition of extracellular matrix components, such as collagen, from fibroblasts moving into the wound space. Consequently, the healing mechanisms of wound significantly varied depending on the presence of such skin deficiency. Successful wound healing requires completing a series of wound healing multistage processes. Since the deletion of one or more of wound healing-related components prevents the wound healing and skin repair, the wound remains exposed. Such an exposed wound can be easily infected, resulting in delayed healing processes, and the formation of ulcers and erosion of skin. There is a need for the development of a drug promoting the growth of granulation tissue and the regeneration of skin on wound involving skin deficiency.
Meanwhile, p43 is a protein consisting of 312 amino acids which is associated with a multi-tRNA synthetase complex to facilitate the catalytic activity of the bound enzyme. The p43 is highly expressed by microneuron in the lesions of autoimmune diseases in vitro including encephalomyelitis, neuritis and uveitis. The phenomenon in which p43 is highly expressed at certain developmental stages and tissues suggests that p43 is related to inflammation response and cell apoptosis (Berger, A. C. et al., J. Immunother. 23:519-527, 2000). We have previously shown that p43 can be employed as an effective cytokine and an anti-tumor agent (PCT International application No. PCT/KR00/00630). However, it is still not shown that p43 may be employed for treating wound. We identified that p43 has a novel activity of promoting wound healing process by acting on the wound healing process comprising the inflammation stage, epithelization stage and angiogenesis stage, and completed the present invention.